REGULATION OF THE PITUITARY-SPECIFIC HOMEOBOX GENE GHF1 BY CELL-AUTONOMOUS AND ENVIRONMENTAL CUES
REGULATION OF THE PITUITARY-SPECIFIC HOMEOBOX GENE GHF1 BY CELL-AUTONOMOUS AND ENVIRONMENTAL CUES
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DOI：
10.1038/345829a0
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发表时间：
1990-06-28
期刊：
影响因子：
64.8
通讯作者：
KARIN, M
中科院分区：
文献类型：
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作者：
MCCORMICK, A;BRADY, H;KARIN, M
HOMEODOMAIN 蛋白 1,2 在酵母中确定交配类型 3、果蝇中分段 4 以及哺乳动物中细胞类型特异性基因表达 5 中发挥作用。在果蝇中，同源盒基因的表达是由调节蛋白和环境线索之间的细胞自主相互作用控制的6-8。类似的控制可能在哺乳动物肢体发育 9,10 和青蛙胚胎发生 11,12 过程中进行。但是，在这些系统中调节同源域蛋白表达的确切方式尚不清楚，需要对同源框基因转录进行生化分析。我们现在描述了对 GHF1 基因的这种分析，该基因编码哺乳动物同源结构域蛋白，指定垂体前叶生长激素细胞中生长激素 (GH) 基因的表达13-15。GHF1 以高度受限的方式转录，GHF1 蛋白的存在在时间和空间上与垂体发育过程中 GH 基因的激活相关。对 GHF1 启动子的分析表明，转录也受到细胞自主相互作用的控制，涉及 GHF1 的正向自动调节，以及调节细胞内环 AMP 水平的环境线索，从而调节 cAMP 反应元件结合蛋白 (CREB)17 的活性，CREB 是一种与 GHF1 启动子结合的普遍存在的反式激活因子。
HOMEODOMAIN proteins1,2function in determination of mating type in yeast3, segmentation in fruit flies4and cell-type specific gene expression in mammals5. InDrosophila, expression of homeobox genes is controlled by cell-autonomous interactions between regulatory proteins and environmental clues6–8. Similar controls may operate during mammalian limb development9,10and frog embryogenesis11,12. But, the exact way in which expression of homeodomain proteins is regulated in these systems is not clear and requires biochemical analysis of homeobox gene transcription. We now describe such an analysis of theGHF1gene, which encodes a mammalian homeodomain protein specifying expression of the growth hormone (GH) gene in anterior pituitary somatotrophs13–15.GHF1is transcribed in a highly restricted manner and the presence of GHF1 protein is correlated both temporally and spatially with activation of theGHgene during pituitary development16. Analysis of theGHF1promoter indicates that transcription is also controlled by cell-autonomous interactions involving positive autoregulation by GHF1, and environmental cues that modulate the intracellular level of cyclic AMP and thereby the activity of cAMP response element binding protein (CREB)17, a ubiquitous transactivator that binds to theGHF1promoter.